Men tend to store fat in visceral adipose tissue in the lower abdomen while pre-menopausal women store fat primarily in peripheral adipose tissue in the hips, buttocks and thighs. As individuals age, sex hormone production declines and is accompanied by an increased storage of fat in visceral adipose tissue. Increased visceral fat is linked to type 2 diabetes, cardiovascular disease and other comorbidities associated with aging. We have discovered a subpopulation of adipocytes (fat cells) that are produced from bone marrow stem cells. These stem cells leave the marrow and travel to fat tissue where they become new fat cells. The bone marrow-derived fat cells accumulate preferentially in female rather than male subjects, and in visceral rather than peripheral adipose tissue. Moreover, the rate at which they accumulate differs from other types of fat cells. These observation have led us to hypothesize that sex hormones may differentially regulate the pro-duction of different adipocyte populations in a depot-specific manner, and thus explain in part differences in fat distribution and function between men and women and changes in fat distribution with aging. This project will test whether loss of sex hormones or their receptors control the production and turn-over of different types of fat cells, and determine if this occurs the same way in both male and female subjects. We will also test whether the production of bone marrow-derived adipocytes is linked factors associated with chronic disease including blood glucose and lipid levels, the production of inflammatory proteins, and insulin responsiveness. Completion of these studies will provide a comprehensive understanding of sex hormones in regulating the production and distribution of distinct adipocyte populations. The results are likely to highlight new targets for controlling the generation of bone marrow-derived adipocytes and other fat cells, and thereby mitigate their harmful effects on health. RELEVANCE (See instructions): Abdominal weight gain increases in men and women as they age is and is a major medical problem with few effective therapies. This project will investigate whether sex hormones control the production of different types of fat cells in different body locations. Successful completion of these studies will identify new targets for controlling the production of harmful fat-storing cells and prevent fat-related chronic disease.